Catching Disease Before It Catches Us

Molecular Imaging helps to diagnose diseases at the cellular level, whether it is cancer, Alzheimer's disease and Parkinson's disease, finds out Shardul Nautiyal

As the focus of medicine shifts from curative to preventive strategies, Molecular Imaging is gaining prominence in diagnostics. Molecular Imaging, a branch of nuclear medicine, studies the physiology of the body at the molecular level for monitoring and detecting evidence for failure or recurrence of disease activity at an early stage. As Dr Inder Talwar, Head, CT and MRI, Bombay Hospital, puts it: "Before any morphological alteration takes place, Molecular Imaging helps to diagnose at the cellular level, whether it is as deadly as cancer of the colon, breast, lung and lymphoma, or neuro-degenerative disorders like Alzheimer's disease and Parkinson's disease."

To which Dr S H Advani, Consultant Oncologist, Jaslok Hospital, adds, "With Molecular Imaging technology, we would be able to obtain information about the changes at genetic level within the tumour cells, which is currently a prominent area of research and development. This will allow us to differentiate between normal and tumour cells. The information from Molecular Imaging will help us to target the tumour cells by targeted therapy."

The diagnostic breakthrough is made possible by the effective use of nuclear medicine tools and modalities employed for Molecular Imaging like Positron Emission Tomography (PET), Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopy (MRS), optical imaging and fusion imaging (PET-CT, PET-MRI and CT-Single Photon Emission Computed Tomography (SPECT)).

"In the next few years, Molecular Imaging will be an essential step in both the study of disease and the process of therapy, drug discovery and delivery" - Dr Atul Marwah,Chief, Nuclear Medicine and PET, Bombay Hospital

Molecular Imaging has two basic applications: diagnostic imaging to determine the location and extent of targeted molecules for the disease being studied, and therapy to treat specific disease-target molecules by adding a therapeutic agent onto the probe.

Discussing the role of a molecular probe, Dr Atul Marwah, Chief, Nuclear Medicine and PET, Bombay Hospital explains, "The ability to tag the molecular probe with a marker molecule to be tracked by a suitable detector outside the body is an crucial characteristic of a molecular probe. This tag can be a radioactive tracer as used in nuclear medicine, or an optically absorbed dye."

Genesis Of Molecular Imaging

Nuclear medicine as of today is re-christened Molecular Imaging. The modus of nuclear medicine specialists to probe into intra-cellular molecules for the diagnosis of disease processes over time has given birth to molecular imaging.

Experts point out that its clinical application to target molecules for effective treatment of disease has popularised the specialty. Spurred by the use of the latest modalities in imaging, research in this field has acquired centre-stage. Today, it has become a subject of research in diagnostics and therapeutics and will prove to be a major breakthrough in the potential treatment of diseases like cancer, in the coming 15 years.

The technology has brought about a revolution not only in the exploration of gene expression and complex body processes, but has also given a boost to gene therapy.

Various Modalities In Molecular Imaging

PET is currently the upcoming modality of Molecular Imaging

Positron Emission Tomography (PET) is currently the upcoming modality of Molecular Imaging. PET is effective in studying the metabolism of different organs. According to a study, distributions of the use of PET are 10 per cent in cases of heart and brain and 80 per cent in cancer diagnosis and follow-up.

Through Molecular Imaging, PET images of the brain can detect Parkinson's disease. A labelled amino-acid (F-DOPA) is used as a tracer in a PET examination in order to determine whether the brain has a deficiency in dopamine synthesis. If it does not, Parkinson's disease can be ruled out and possible tremors in the patient's muscles will be treated differently.

"In the case of Alzheimer's disease, Molecular Imaging through PET brain scans shows a very consistent pattern where certain brain regions have low metabolism at the early stages of the disease. This allows early detection much before diagnosis can be confirmed by a physician" - Dr Viswanathan Iyer, Brain and Spine Surgeon, Bombay Hospital

"Similarly, in the case of Alzheimer's disease, Molecular Imaging through PET brain scans shows a very consistent pattern where certain brain regions have low metabolism at the early stages of the disease. This allows early detection much before diagnosis can be confirmed by a physician," says Dr Iyer Viswanathan, Brain and Spine Surgeon, Bombay Hospital.

PET Imaging with the radiotracer fluorodeoxyglucose (FDG) is a promising tool in detecting Alzheimer's disease in patients who have mild cognitive impairment (MCI), according to a study reported in the October issue of the Society of Nuclear Medicine's Journal of Nuclear Medicine.

MRI and CT

Another important modality in Molecular Imaging is MRI. Informs Dr Vikram Lele, Chief, Nuclear Medicine, Jaslok Hospital, "MR spectroscopy is an important tool of molecular imaging. It is based on the quantification of molecules through analysis of the spectra achieved during the imaging process. This helps to determine the molecular composition of tissues in health and disease."

Advanced MR Imaging equipment is in use today of the order of 1.5 Tesla to 3.0 Tesla for routine MRI. Moreover, 20 Tesla MRIs are also employed for research. One of the most commonly used tools of Molecular Imaging is Blood Oxygen Level Dependent (BOLD) imaging, based on the theory that haem (iron) component of the blood is measured by the susceptibility of the MRI. MRI can detect oxygen, a compound in the cortex area, for example, motor cortex, visual cortex and the sensory cortex depending on different kinds of stimuli, leading to potential expansion of Molecular Imaging.

Besides this, other Molecular Imaging techniques like perfusion MRI and perfusion CT give functional evaluation. The major application of MRI is in strokes where through diagnosis of the infracted brain, the reversible region of the brain can be treated.

Another major application of Molecular Imaging in MRI is the grading of tumours. Grading of tumours is an important application of perfusion MRI and perfusion CT. Molecular Imaging studies show that chances of survival are less in high-grade tumours whereas prognosis is good in low-grade tumours. Moreover, perfusion MRI and perfusion CT as important techniques of molecular imaging are effective tools to distinguish between radiation necrosis and tumour recurrence.

Research In Molecular Imaging

A new area of research which has inspired neurologists and NM experts is Receptor Imaging. "Receptor Imaging implies that various neuro-chemicals act through receptors. Every cell has several receptors. Receptor Imaging involves attaching a compound to the Positron Emitting Isotope (PEI) and targeting it to the respective receptor, which in turn will help determine the localisation of the receptors leading to identification of tumours. It will also help in studying deficiency and excess states of receptors, study drug actions at receptor levels and in drug discovery," explains Dr Lele.

To cite an example, substantial progress has been made in the dopamine receptor studies in the west, especially in the US. Three new drugs called Choline Esterase Inhibitors helpful in treating memory loss in Alzheimer's disease have been launched in the market. Experts foresee this technology coming to India within a year's time.

With PET, it is possible to measure the effects of these drugs on the brain. Amyloid deposits, which occur in the brain in Alzheimer's disease, can also be imaged with PET, giving early diagnosis at cellular level. Molecular Imaging has now also been able to detect apoptosis, which implies programmed cell death. Now with the help of Molecular Imaging, one can detect the possibility of cell death and suggest solutions to reverse it. This is made possible by attaching Annexin (V) to an isotope, which targets phosphatidyl Serine expressed on cells undergoing apoptosis.

The technology also has uses in diagnosing unstable plaque. Plaques form in the inner lining of the arteries, which leads to narrowing of arteries and heart attacks (atherosclerosis). Unstable plaque is a dangerous combination of macrophages and lipids, detectable through FDG and MR technique, which are the latest tools of molecular imaging.

Studies in the west have shown that somatostatin receptors have been expressed on several tumours. These receptors can be imaged using radiolabelled Octreotide. Positive tumours can be destroyed by high-energy labelled Octreotide, achieving targeted diagnosis as well as therapy.

"Yet another interesting area of Molecular Imaging is the use of optical imaging in hypoxia imaging, which gives the degree of oxygen starvation in blood perfused tissue. This can be used to infer the presence of malignant tissue growth," explains Dr Marwah.

Issues In Molecular Imaging

Experts point out that though PET is the latest modality in the field of Molecular Imaging, the technology is not cost-effective. Setting up a dedicated PET camera costs around Rs 9 crore while a Gamma PET camera costs around Rs 3 crore. The cyclotron which produces radio-pharmaceutical material for PET scans adds about Rs 12 to Rs 15 crore to the cost. A cyclotron is required in the vicinity of the PET scanner as the radioactive substance produced by the cyclotron has a short half-life.

The cost of a PET scan in a hospital ranges from Rs 8,000 to Rs 12,000, which is very high. "The patient is left with no money for treatment, when his entire amount has gone into scanning the disease," Dr Lele explains.

The harsh reality is that despite its benefits, molecular imaging has very few takers. "There is no availability of the facility and thus no awareness amongst the patients and hence the demand is less," says Dr Talwar. Tata Memorial Hospital, Mumbai registers only 18 cases of Molecular Imaging daily having a dedicated PET camera while Jaslok Hospital having Gamma PET camera registers only two cases per day.

What The Future Holds

PET imaging being the latest modality is just the tip of the iceberg in the vast field of Molecular Imaging. With newer tracers and other modalities, the imaging of specific proteins or pathways will go beyond, allowing clinicians to tailor therapies for better drug selection and non-invasive monitoring of molecular events.

"In the next few years, Molecular Imaging will be an essential step in both the study of disease and the process of therapy, drug discovery and delivery," predicts Dr Marwah. Companies like GE, Siemens, Philips and IBA are manufacturing equipment for Molecular Imaging like PET cameras and cyclotrons.

shardulnautiyal@rediffmail.com